ICHISE Nobutoshi

写真a

Affiliation

School of Medicine, Department of Physiology

Job title

Lecturer
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Education 【 display / non-display 】

  • 1996
    -
    2003

    Hokkaido University   Graduate School of Environmental Earth Science   環境分子生物学講座  

  • 1991
    -
    1995

    Hokkaido University   School of Fisheries Sciences   水産増殖学科  

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Degree 【 display / non-display 】

  • 北海道大学   博士（地球環境科学）

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Professional Memberships 【 display / non-display 】

  • 　
    　
    　

    THE PHYSIOLOGICAL SOCIETY OF JAPAN

  • 　
    　
    　

    JAPANESE HEART RHYTHM SOCIETY

  • 　
    　
    　

    THE SOCIETY FOR BIOTECHNOLOGY, JAPAN

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Research Areas 【 display / non-display 】

  • Life sciences   Physiology  

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Affiliation 【 display / non-display 】

  • Sapporo Medical University   医学部細胞生理学講座   Assistant Professor  

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Research Interests 【 display / non-display 】

  • 興奮収縮連関

  • 心臓原基

  • 発生

  • 筋肉生理学

  • サルコメア

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Papers 【 display / non-display 】

  • Platelet-rich plasma does not accelerate the healing of damaged muscle following muscle strain.

    Hiroyori Fusagawa, Takashi Yamada, Tatsuya Sato, Yuki Ashida, Atsushi Teramoto, Hiroyuki Takashima, Azuma Naito, Nao Tokuda, Nao Yamauchi, Nobutoshi Ichise, Izaya Ogon, Toshihiko Yamashita, Noritsugu Tohse

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society    2024.01  [Refereed]  [International journal]

    　View Summary

    Although platelet-rich plasma (PRP) has been widely used regardless of the severity of muscle strain, there have been very few basic studies in which its effects on muscle injury were examined by using models that accurately mimic the clinical muscle strain injury process. Therefore, the aim of this study was to confirm by physiological and structural analyses whether PRP purified by a general preparation method has a muscle healing effect on muscle damage caused by eccentric contraction (ECC). Male Wistar rats were subjected to muscle injury induced by ECC in bilateral plantar flexor muscles using electrical stimulation and an automatically dorsiflexing footplate. The rats were randomly assigned to three groups by type of injection: phosphate-buffered saline (PBS), leukocyte-poor PRP (LP-PRP), or leukocyte-rich PRP (LR-PRP) injection into gastrocnemius muscles three times at weekly intervals. The platelet concentrations of the LP-PRP and LR-PRP were three to five times higher than that of whole blood. The recovery process of torque strength in the plantar flexor muscle, signal changes in MRI images, and histological evaluation 3 weeks after injury showed no obvious differences among the three groups, and every muscle recovered well from the injury without marked fibrosis. The results that neither LP-PRP nor LR-PRP was found to accelerate healing of muscle injuries suggested that conventional preparation and use of PRP for simple muscle injuries caused by muscle strain should be carefully considered, and further basic research using models that accurately mimic clinical practice should be carried out to determine the optimal use of PRP.

    DOI PubMed

  • High-intensity interval training using electrical stimulation ameliorates muscle fatigue in chronic kidney disease-related cachexia by restoring mitochondrial respiratory dysfunction.

    Hiroyori Fusagawa, Tatsuya Sato, Takashi Yamada, Azuma Naito, Nao Tokuda, Nao Yamauchi, Nobutoshi Ichise, Toshifumi Ogawa, Takuro Karaushi, Atsushi Teramoto, Noritsugu Tohse

    Frontiers in physiology   15   1423504 - 1423504  2024  [Refereed]  [International journal]

    　View Summary

    BACKGROUND: Exercise, especially high-intensity interval training (HIIT), can increase mitochondrial respiratory capacity and enhance muscular endurance, but its systemic burden makes it difficult to safely and continuously prescribe for patients with chronic kidney disease (CKD)-related cachexia who are in poor general condition. In this study, we examined whether HIIT using electrical stimulation (ES), which does not require whole-body exercise, improves muscle endurance in the skeletal muscle of 5/6 nephrectomized rats, a widely used animal model for CKD-related cachexia. METHODS: Male Wistar rats (10 weeks old) were randomly assigned to a group of sham-operated (Sham) rats and a group of 5/6 nephrectomy (Nx) rats. HIIT was performed on plantar flexor muscles in vivo with supramaximal ES every other day for 4 weeks to assess muscle endurance, myosin heavy-chain isoforms, and mitochondrial respiratory function in Nx rats. A single session was also performed to identify upstream signaling pathways altered by HIIT using ES. RESULTS: In the non-trained plantar flexor muscles from Nx rats, the muscle endurance was significantly lower than that in plantar flexor muscles from Sham rats. The proportion of myosin heavy chain IIa/x, mitochondrial content, mitochondrial respiratory capacity, and formation of mitochondrial respiratory supercomplexes in the plantaris muscle were also significantly decreased in the non-trained plantar flexor muscles from Nx rats than compared to those in plantar flexor muscles from Sham rats. Treatment with HIIT using ES for Nx rats significantly improved these molecular and functional changes to the same degrees as those in Sham rats. Furthermore, a single session of HIIT with ES significantly increased the phosphorylation levels of AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK), pathways that are essential for mitochondrial activation signaling by exercise, in the plantar muscles of both Nx and Sham rats. CONCLUSION: The findings suggest that HIIT using ES ameliorates muscle fatigue in Nx rats via restoration of mitochondrial respiratory dysfunction with activation of AMPK and p38 MAPK signaling. Our ES-based HIIT protocol can be performed without placing a burden on the whole body and be a promising intervention that is implemented even in conditions of reduced general performance status such as CKD-related cachexia.

    DOI PubMed

  • Skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-CoA during muscle fatigue in 5/6 nephrectomized rats.

    Hiroyori Fusagawa, Tatsuya Sato, Takashi Yamada, Yuki Ashida, Iori Kimura, Azuma Naito, Nao Tokuda, Nao Yamauchi, Nobutoshi Ichise, Yoshinori Terashima, Izaya Ogon, Atsushi Teramoto, Toshihiko Yamashita, Noritsugu Tohse

    Journal of applied physiology (Bethesda, Md. : 1985)    2023.08  [Refereed]  [International journal]

    　View Summary

    Chronic kidney disease (CKD)-related cachexia increases the risks of reduced physical activity and mortality. However, the physiological phenotype of skeletal muscle fatigue and changes in intramuscular metabolites during muscle fatigue in CKD-related cachexia remain unclear. In the present study, we performed detailed muscle physiological evaluation, analysis of mitochondrial function, and comprehensive analysis of metabolic changes before and after muscle fatigue in a 5/6 nephrectomized rat model of CKD. Wistar rats were randomized to a sham-operation (Sham) group that served as a control group or a 5/6 nephrectomy (Nx) group. Eight weeks after the operation, in situ torque and force measurements in plantar flexor muscles in Nx rats using electrical stimulation revealed a significant decrease in muscle endurance during subacute phase related to mitochondrial function. Muscle mass was reduced without changes in the proportions of fiber type-specific myosin heavy chain isoforms in Nx rats. Pyruvate-malate-driven state 3 respiration in isolated mitochondria were impaired in Nx rats. Protein expression levels of mitochondrial respiratory chain complexes III and V were decreased in Nx rats. Metabolome analysis revealed that the increased supply of acetyl CoA in response to fatigue was blunted in Nx rats. These findings suggest that CKD deteriorates skeletal muscle endurance in association with mitochondrial dysfunction and inadequate supply of acetyl-CoA during muscle fatigue.

    DOI PubMed

  • Enhanced glucose metabolism through activation of HIF-1α covers the energy demand in a rat embryonic heart primordium after heartbeat initiation.

    Tatsuya Sato, Nobutoshi Ichise, Takeshi Kobayashi, Hiroyori Fusagawa, Hiroya Yamazaki, Taiki Kudo, Noritsugu Tohse

    Scientific reports   12 ( 1 ) 74 - 74  2022.01  [Refereed]  [International journal]

    Authorship：   Lead author

    　View Summary

    The initiation of heartbeat is an essential step in cardiogenesis in the heart primordium, but it remains unclear how intracellular metabolism responds to increased energy demands after heartbeat initiation. In this study, embryos in Wistar rats at embryonic day 10, at which heartbeat begins in rats, were divided into two groups by the heart primordium before and after heartbeat initiation and their metabolic characteristics were assessed. Metabolome analysis revealed that increased levels of ATP, a main product of glucose catabolism, and reduced glutathione, a by-product of the pentose phosphate pathway, were the major determinants in the heart primordium after heartbeat initiation. Glycolytic capacity and ATP synthesis-linked mitochondrial respiration were significantly increased, but subunits in complexes of mitochondrial oxidative phosphorylation were not upregulated in the heart primordium after heartbeat initiation. Hypoxia-inducible factor (HIF)-1α was activated and a glucose transporter and rate-limiting enzymes of the glycolytic and pentose phosphate pathways, which are HIF-1α-downstream targets, were upregulated in the heart primordium after heartbeat initiation. These results suggest that the HIF-1α-mediated enhancement of glycolysis with activation of the pentose phosphate pathway, potentially leading to antioxidant defense and nucleotide biosynthesis, covers the increased energy demand in the beating and developing heart primordium.

    DOI PubMed

  • Ultrastructural Assessment and Proteomic Analysis in Myofibrillogenesis in the Heart Primordium After Heartbeat Initiation in Rats.

    Nobutoshi Ichise, Tatsuya Sato, Hiroyori Fusagawa, Hiroya Yamazaki, Taiki Kudo, Izaya Ogon, Noritsugu Tohse

    Frontiers in physiology   13   907924 - 907924  2022  [Refereed]  [International journal]

    Authorship：   Lead author

    　View Summary

    Myofibrillogenesis is an essential process for cardiogenesis and is closely related to excitation-contraction coupling and the maintenance of heartbeat. It remains unclear whether the formation of myofibrils and sarcomeres is associated with heartbeat initiation in the early embryonic heart development. Here, we investigated the association between the ultrastructure of myofibrils assessed by transmission electron microscopy and their proteomic profiling assessed by data-independent acquisition mass spectrometry (DIA-MS) in the rat heart primordia before and after heartbeat initiation at embryonic day 10.0, when heartbeat begins in rats, and in the primitive heart tube at embryonic day 11.0. Bundles of myofilaments were scattered in a few cells of the heart primordium after heartbeat initiation, whereas there were no typical sarcomeres in the heart primordia both before and after heartbeat initiation. Sarcomeres with Z-lines were identified in cells of the primitive heart tube, though myofilaments were not aligned. DIA-MS proteome analysis revealed that only 43 proteins were significantly upregulated by more than 2.0 fold among a total of 7,762 detected proteins in the heart primordium after heartbeat initiation compared with that before heartbeat initiation. Indeed, of those upregulated proteins, 12 (27.9%) were constituent proteins of myofibrils and 10 (23.3%) were proteins that were accessories and regulators for myofibrillogenesis, suggesting that upregulated proteins that are associated with heartbeat initiation were enriched in myofibrillogenesis. Collectively, our results suggest that the establishment of heartbeat is induced by development of bundles of myofilaments with upregulated proteins associated with myofibrillogensis, whereas sarcomeres are not required for the initial heartbeat.

    DOI PubMed

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Books and Other Publications 【 display / non-display 】

  • 産学官連携の「質」の向上方策に関する調査研究報告書

    ( Part： Contributor)

    新技術振興渡辺記念会  2009.05

  • 産学官連携コーディネーターの成功・失敗事例に学ぶー産学官連携の新たな展開に向けてー

    ( Part： Edit)

    文部科学省研究振興局研究環境産業連携課  2006.06

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Misc 【 display / non-display 】

  • Roles of mitochondria in energy metabolism after heartbeat initiation in the heart primordium of the rat embryo

    Tatsuya Sato, Nobutoshi Ichise, Toshifumi Ogawa, Takuro Karaushi, Hiroyori Fusagawa, Taiki Kudo, Noritsugu Tohse

    The 10th FAOPS congress.    2023.11  [Refereed]

    Research paper, summary (international conference)  

  • Assessment of myofibrillogenesis in rat embryonic hearts in the initiation of heartbeats by transmission electron microscopy and evaluation of its molecular expression patterns by proteomic analysis.

    NOBUTOSHI ICHISE, TATSUYA SATO, TAKURO KARAUSHI, HIROYORI FUSAGAWA, TAIKI KUDO, NORITSUGU TOHSE

    JOURNAL OF PHYSIOLOGICAL SCIENCES   73 ( Supplement 1 ) 154 - 154  2023.05

    Authorship：   Lead author

  • Proteomic analysis of the metabolic pathway involved in the developmental process of cardiac primordium just after heartbeat initiation to primordial heart tube formation in rats.

    TAKURO KARAUSHI, Tatsuya Sato, Nobutoshi Ichise, Hiroyori Fusagawa, Taiki Kudo, Noritsugu Tohse

    JOURNAL OF PHYSIOLOGICAL SCIENCES   73 ( Supplement 1 ) 98 - 98  2023.05

  • Effect of high-intensity interval training using electrical stimulation on mitochondrial dysfunction and muscle fatigue in 5/6 nephrectomy rat model of chronic kidney disease

    Hiroyori Fusagawa, Takashi Yamada, Tatsuya Sato, Yuki Ashida, Azuma Naito, Nao Tokuda, Nao Yamauchi, Nobutoshi Ichise, Takuro Karaushi, Atsushi Teramoto, Toshihiko Yamashita, Noritsugu Tohse

    JOURNAL OF PHYSIOLOGICAL SCIENCES   73 ( Supplement 1 ) 99 - 99  2023.05

  • Mechanism of metabolic adaptation in the heart primordium just after heartbeat initiation in the early embryonic development in rats

    TATSUYA SATO, NOBUTOSHI ICHISE, HIROYORI FUSAGAWA, TAKURO KARAUSHI, TAIKI KUDO, NORITSUGU TOHSE

    JOURNAL OF PHYSIOLOGICAL SCIENCES   73 ( Supplement 1 ) 106 - 106  2023.05

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Research Projects 【 display / non-display 】

  • 低酸素誘導因子1α が胎生初期心臓原基の拍動開始および拍動維持に及ぼす影響の検討

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2022.04
    -
    2025.03
     

    當瀬 規嗣, 佐藤 達也, 一瀬 信敏

  • A study of mitochondrial function on the mechanisms of heartbeat initiation in embryonic heart

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2019.04
    -
    2022.03
     

    Noritsugu Tohse

    Authorship： Coinvestigator(s)

    　View Summary

    The initiation of heartbeat is an essential step in cardiogenesis in the heart primordium, but it remains unclear how intracellular metabolism responds to increased energy demands after heartbeat initiation. Myofibrillogenesis is an essential process for cardiogenesis and is closely related to excitation-contraction coupling and the maintenance of heartbeat. However, how myofibrils and sarcomeres are associated with heartbeat initiation in the early embryonic heart development also remains unclear. In our study, it is suggested that the HIF-1α-mediated enhancement of glycolysis with activation of the pentose phosphate pathway, potentially leading to antioxidant defense and nucleotide biosynthesis, covers the increased energy demand in the beating heart. And it is also suggested that heartbeat initiation can be induced by development of bundles of myofilaments with up-regulated proteins associated with myofibrillogensis, whereas sarcomeres are not required for the initial heartbeat.

  • Analysis of mechanisms of heartbeat initiation in embryonic stage

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2010
    -
    2012
     

    TOHSE Noritsugu, KOBAYASHI Takeshi, MADEA Sachiko, ICHISE Nobutoshi

    Authorship： Coinvestigator(s)

    　View Summary

    In early embryonic stage, rat heart primordium begins the heatbeating. In cardiomyocytes from the early primordium, calcium current was observed. The calcium current was activated in pacemaker potential, and may be related to automaticity of heart. During this embryonic stage, gene expression and construction of protein molecule for the calcium channel (Cav1.3) were observed. The Cav 1.3 channels may be determinant for initiation of heart beat.

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Teaching Experience 【 display / non-display 】

  • 解剖生理学IV  

    札幌看護医療専門学校  

    2024
    -
    Now
     

  • 生態機能形態学II   ( Postgraduate )

    札幌医科大学大学院  

    2021
    -
    Now
     

  • 細胞・器官生理学  

    札幌医科大学  

    2019
    -
    Now
     

  • 生理学  

    吉田学園医療歯科専門学校  

    2017
    -
    Now
     

  • 医学概論・医療総論３（地域滞在実習）  

    Sapporo Medical University  

    2016
    -
    Now
     

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Committee Memberships 【 display / non-display 】

  • 2024.09
    -
    Now

      Review Editor, Frontiers in Cardiovascular Medicine

  • 2015
    -
    Now

      評議員

  • 2014.04
    -
    2016.03

      事務局長

  • 2008.04
    -
    2009.03

      委員

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Social Activities 【 display / non-display 】

  • 知的財産の活用による社会貢献

    室蘭市立室蘭看護専門学院 

    2008.01
    　
    　

  • 大学の知財

    北海道東海大学 

    2006.06
    　
    　

  • 人に役立つ微生物たち

    室蘭市立室蘭看護専門学院 

    2004.07
    　
    　

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